Growth Factor Sensitive Vesicle

ABSTRACT

A generally spherical growth factor sensitive vesicle bearing growth factor receptors ( 12 ) having chemical compounds ( 14 ) covalently cross-linked to their non-growth factor binding domains. The chemical compounds are capable of associating to form larger chemical compounds ( 16 ) capable of destabilizing the vesicle. Methods for treating growth factor-overexpressing neoplasms are disclosed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of provisional patent applicationSer. No. 61/126,255, filed May 2, 2008 by the present inventor.

FEDERALLY SPONSORED RESEARCH

Not Applicable

SEQUENCE LISTING OR PROGRAM

Not Applicable

BACKGROUND OF THE INVENTION

1. Field of Invention

This invention generally relates to vesicular systems, specifically to agrowth factor-sensitive vesicle.

2. Prior Art

Currently, conventional treatments for growth factor-overexpressingneoplasms are generally limited to surgery, radiation therapy, andgeneralized chemotherapy. Radiation therapy and generalized chemotherapymay result in significant side effects, including an increased risk ofnew tumor formation. Surgery, when feasible, is attendant with the riskof various surgical complications. Furthermore, combinations oftreatments, usually radiation therapy and generalized chemotherapy, andrecurring treatments, such as recurring radiation therapy, are oftennecessary, typically resulting in additional side effects and/or sideeffects of greater severity.

To achieve the goal of maximizing the effectiveness of chemotherapywhile simultaneously minimizing undesirable systemic side effects, theideal solution would be to use targeted drug delivery to releasechemotherapeutic agents specifically in the neighborhood of growthfactor-overexpressing neoplasms. Such targeted drug delivery wouldfacilitate chemotherapeutic treatment of the neoplasms by minimizingsystemic drug exposure (and hence potentially toxic systemic sideeffects) while simultaneously maximizing drug exposure to the neoplasms.

A method for such targeted drug delivery that has been researched andused extensively involves the use of vesicles sensitive to artificiallygenerated factors such as ultrasound. However, vesicles sensitive tofactors such as ultrasound are typically attendant with theinconvenience and cost associated with the use of external medicalequipment, such as an ultrasound machine. Also, it is not always clear,such as in the case of metastatic tumors (where the tumors' preciselocations may be unknown), where the factor (for example, ultrasoundwaves) should be directed.

Since the goal is to treat growth factor-overexpressing neoplasms, theideal method for targeted drug delivery would involve the use ofvesicles sensitive to abnormal (or excessive) amounts of growth factors(that is, growth factor sensitive vesicles). Such growth factorsensitive vesicles would be of great clinical significance because theycould be used to specifically release chemotherapeutic agents in theneighborhood of growth factor-overexpressing neoplasms. However, due tothe technical challenges inherent in creating a vesicle sensitive togrowth factors, no such vesicles have previously been developed. Thetechnical challenges in creating such a vesicle arise because, unlikefactors such as ultrasound waves, growth factors do not have the abilityto directly destabilize a vesicle.

As such, there is no relevant prior art pertaining to the growth factorsensitive vesicle of the invention.

3. Objects and Advantages

Accordingly, several objects and advantages of the invention are:

-   -   (a) to provide a growth factor sensitive vesicle which can carry        and deliver a wide variety of chemotherapeutic and other        pharmaceutical agents;    -   (b) to provide a growth factor sensitive vesicle which can be        easily manufactured in a wide variety of external and internal        dimensions;    -   (c) to provide a growth factor sensitive vesicle which can have        a wide variety of vesicle compositions;    -   (d) to provide a growth factor sensitive vesicle which can have        a wide variety of vesicle surface modifications; and    -   (e) to provide a growth factor sensitive vesicle which can        simultaneously be sensitive to other factors, such as        ultrasound.

Further objects and advantages will become apparent from a considerationof the ensuing description and drawings.

SUMMARY

In accordance with the present invention a growth factor sensitivevesicle comprises a generally spherical closed body bearing growthfactor receptors having chemical compounds covalently cross-linked totheir non-growth factor binding domains.

DRAWINGS—FIGURES

A brief description of the invention is hereafter described bynon-limiting examples.

FIG. 1 shows a cross-sectional view of a growth factor sensitivevesicle.

FIG. 2 shows a cross-sectional view of a similar growth factor sensitivevesicle with an internal shell.

FIG. 3 shows a cross-sectional view of a similar growth factor sensitivevesicle with growth factor receptors bound to the external face of theexternal shell of the vesicle.

FIG. 4 shows a cross-sectional view of a growth factor sensitive vesiclewith growth factors bound to the growth factor receptors.

FIG. 5 shows a cross-sectional view of a growth factor sensitive vesiclewith a destabilized external shell.

DRAWINGS—REFERENCE NUMERALS

-   -   10—vesicle    -   12—growth factor receptor    -   14—chemical compound    -   16—larger chemical compound    -   18—growth factor    -   20—external shell    -   22—internal shell

DETAILED DESCRIPTION—FIG. 1—PREFERRED EMBODIMENT

While this invention may be embodied in many different forms, there aredescribed in detail herein specific embodiments of the invention. Thisdescription is an exemplification of the principles of the invention andis not intended to limit the invention to the particular embodimentsillustrated.

Turning now to the figures, a preferred embodiment of the growth factorsensitive vesicle of the present invention is illustrated in FIG. 1(cross-sectional view). The vesicle 10 has growth factor receptors 12,covalently cross-linked to chemical compounds 14, incorporated into theexternal shell 20 of the vesicle 10. Pharmaceutical agents may be boundto the external shell, the growth factor receptors, or the chemicalcompounds. Pharmaceutical agents may also be incorporated into theexternal shell, or encapsulated within the external shell. In thepreferred embodiment, the external shell is a phospholipid bilayer.However, the external shell can consist of any other material that canform a generally spherical closed body. Also, additional chemicalcompounds may be cross-linked to the growth factor receptors, andadditional growth factor receptors may be incorporated into the externalshell.

Operation—FIGS. 4 and 5

A growth factor sensitive vesicle 10, in the preferred embodiment, withgrowth factors 18 bound to the growth factor receptors 12 is illustratedin FIG. 4 and FIG. 5; in each case a cross-sectional view is shown.

As shown in FIG. 4, when growth factors 18 are bound to the growthfactor receptors 12, dimerization of the growth factor receptors 12occurs, resulting in the chemical compounds 14 (not shown here but shownin FIG. 1) associating to form a larger chemical compound 16 capable ofdestabilizing the external shell 20 of the vesicle 10. Then, as shown inFIG. 5, the larger chemical compound 16 interacts with and destabilizesthe external shell 20 of the vesicle 10, resulting in the release of anypharmaceutical agents carried by the vesicle 10.

FIGS. 2-3—Additional Embodiments

Additional embodiments are shown in FIG. 2 and FIG. 3; in each case across-sectional view is illustrated.

In FIG. 2 the vesicle 10 has an internal shell 22 in addition to anexternal shell 20 with incorporated growth factor receptors 12covalently cross-linked to chemical compounds 14. Pharmaceutical agentsmay be bound to the external shell, the internal shell, the growthfactor receptors, or the chemical compounds. Pharmaceutical agents mayalso be incorporated into the external shell or the internal shell, orencapsulated within the external shell or the internal shell. Additionalinternal shells may be encapsulated within the external shell. Also,additional chemical compounds may be cross-linked to the growth factorreceptors, and additional growth factor receptors may be incorporatedinto the external shell. Please note that this is only one of a widevariety of possible additional embodiments of the vesicle.

In FIG. 3 the vesicle 10 has growth factor receptors 12, covalentlycross-linked to chemical compounds 14, bound to the external face of theexternal shell 20 of the vesicle. Pharmaceutical agents may be bound tothe external shell, the growth factor receptors, or the chemicalcompounds. Pharmaceutical agents may also be incorporated into theexternal shell, or encapsulated within the external shell. Additionalchemical compounds may be cross-linked to the growth factor receptors.Additional growth factor receptors may be bound to the external shell.Also, additional growth factor receptors may be incorporated into theexternal shell. Please note that this is only one of a wide variety ofpossible additional embodiments of the vesicle.

Advantages

From the description above, a number of advantages of the growth factorsensitive vesicle of the invention become evident:

-   -   (a) The growth factor sensitive vesicle can be used to carry and        deliver a wide variety of pharmaceutical agents specifically in        the neighborhood of growth factor-overexpressing neoplasms.    -   (b) The growth factor sensitive vesicle can be made easily at a        wide variety of external and internal dimensions without        altering any aspect of its design.    -   (c) The use of vesicle-borne growth factor receptors to provide        vesicle sensitivity to abnormal amounts of growth factors        permits a wide variety of vesicle compositions and vesicle        surface modifications.    -   (d) The use of vesicle-borne growth factor receptors to provide        vesicle sensitivity to abnormal amounts of growth factors        further permits simultaneous vesicle sensitivity to other        factors, such as ultrasound, if desired.

CONCLUSIONS, RAMIFICATIONS, AND SCOPE

Accordingly, the reader will see that the growth factor sensitivevesicle of the invention allows all of the benefits associated with theuse of a non-growth factor sensitive vesicle while presentingsignificant additional advantages. It can be used to carry and deliver awide variety of pharmaceutical agents. It can be easily manufacturedwith a wide variety of external and internal dimensions, vesiclecompositions, and vesicle surface modifications. Most importantly, itcan be used to specifically release pharmaceutical agents in theneighborhood of growth factor-overexpressing neoplasms. Furthermore, thegrowth factor sensitive vesicle of the invention can simultaneously besensitive to other factors, such as ultrasound.

The above disclosure is intended for illustrative purposes only and isnot exhaustive. From the foregoing description, one skilled in the artcan readily ascertain the essential characteristics of the inventionand, without departing from the spirit and scope thereof, can adapt theinvention to various usages and conditions. Changes in the form andsubstitution of equivalents are contemplated as circumstances maysuggest or render expedient, and although specific terms have beenemployed herein, they are intended in a descriptive sense and not forpurposes of limitation. Furthermore, any theories attempting to explainthe mechanism of actions have been advanced merely to aid in theunderstanding of the invention and are not intended as limitations.

Thus the scope of the invention should be determined by the appendedclaims and their legal equivalents, rather than by the examples given.

1. A growth factor sensitive vesicle, comprising: an external shellwhich defines a generally spherical closed body; said shell bearing atleast two growth factor receptors having functional growth factorbinding domains facing outside said shell, at least two of said growthfactor receptors each having at least one non-growth factor bindingdomain covalently cross-linked to at least one chemical compound, atleast two of the chemical compounds being capable of associating to forma chemical compound capable of destabilizing said shell.
 2. The growthfactor sensitive vesicle of claim 1, wherein said growth factorsensitive vesicle is selected from a group consisting of an artificialcell, a liposome, a niosome, a polymersome, and a vesosome.
 3. Thegrowth factor sensitive vesicle of claim 1, wherein said chemicalcompound capable of destabilizing said shell is a surface active agent.4. A method for treating a growth factor-overexpressing neoplasmcomprising administering an effective amount of the growth factorsensitive vesicle of claim
 1. 5. The method of claim 4, wherein saidgrowth factor-overexpressing neoplasm is a growth factor-overexpressingcancer.
 6. The method of claim 4, wherein said growthfactor-overexpressing neoplasm is a growth factor-overexpressingmalignant tumor.
 7. A method for treating a growth factor-overexpressingneoplasm comprising administering an effective amount of the growthfactor sensitive vesicle of claim
 2. 8. The method of claim 7, whereinsaid growth factor-overexpressing neoplasm is a growthfactor-overexpressing cancer.
 9. The method of claim 7, wherein saidgrowth factor-overexpressing neoplasm is a growth factor-overexpressingmalignant tumor.
 10. A method for treating a growthfactor-overexpressing neoplasm comprising administering an effectiveamount of the growth factor sensitive vesicle of claim
 3. 11. The methodof claim 10, wherein said growth factor-overexpressing neoplasm is agrowth factor-overexpressing cancer.
 12. The method of claim 10, whereinsaid growth factor-overexpressing neoplasm is a growthfactor-overexpressing malignant tumor.